Methylenetetrahydrofolate Reductase Mutation and Coronary Artery Disease

To the Editor: The article by Kluijtmans and colleagues1 ( Circulation , October 21, 1997) adds to the growing literature on the relationship between the common thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) and risk of vascular disease. In an angiographically assessed cohort of subjects with coronary artery disease (CAD) participating in a statin regression trial (REGRESS), significantly increased homocysteine concentrations were found in subjects homozygous (+/+) or heterozygous (+/−) for the thermolabile variant compared with those carrying only the normal variant (−/−). Median levels were 2.8 and 0.8 μmol/L higher in the +/+ and +/− subjects, respectively. Compared with population-based controls, there was trend toward higher risk of CAD in subjects carrying the thermolabile variant, but this did not reach significance (OR for +/+ versus −/−: 1.21 [0.87 to 1.68]; +/− versus −/−: 1.14 [0.94 to 1.38]). However, when the results were combined with those of 6 other studies, including our own,2 in a meta-analysis, there was a significant increase in relative risk in subjects with the +/+ genotype (OR, …